Decrease of CD4+FOXP3+ T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor
Decrease of CD4+FOXP3+ T regulatory cells in the peripheral blood of human subjects undergoing a mental stressor
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DOI：
10.1016/j.psyneuen.2009.10.005
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发表时间：
2010-06-01
影响因子：
3.7
通讯作者：
Atanackovic, Djordje
中科院分区：
文献类型：
--
作者：
Freier, Eva;Weber, Cora Stefanie;Atanackovic, Djordje
我们之前已经证明，急性心理应激会提醒适应性免疫反应，导致外周血液中抗原经验的效应器T细胞增加。T调节细胞(Tregs)在维持自身耐受和控制自身免疫反应中起核心作用。在这里，我们首次在应激诱导的适应性免疫反应激活的背景下分析了Treg的行为。31名健康的年轻男性接受了短暂的实验室应激源，并在交叉设计中作为他们自己的非应激对照。我们用流式细胞术量化了急性应激对CD4(+)FOXP3(+)T调节细胞和其他T细胞亚群的影响。此外，我们还分析了受试者外周T细胞中Treg相关效应分子和应激激素受体的表达。我们证实了先前观察到的应激导致CD45RA(+)CCR7(+)“幼稚”和CD45RA(-)CCR7(+)“中央记忆”T细胞减少，而CD45RA(-)-CCR7(-)“记忆效应”和CD45RA(+)CCR7(-)“终末分化”效应T细胞保持稳定或增加。重要的是，我们发现急性心理应激会导致CD4(+)FOXP3(+)Tregs和表达Treg相关效应分子细胞毒性T淋巴细胞抗原-4(CTLA-4)和潜伏期相关肽(LAP)的CD4(+)T细胞相应减少。最后，我们观察到β(1)-肾上腺素能和糖皮质激素a受体在Treg中过表达，这表明这些分子可能介导了对Treg的应激相关效应。在慢性应激的情况下，这种情况可能会导致自身免疫性疾病等炎症状况的恶化。(C)2009爱思唯尔有限公司。保留所有权利。
We have previously shown that acute psychological stress alerts the adaptive immune response causing an increase in antigen-experienced effector T cells in the peripheral blood. T regulatory cells (Tregs) play a central role in maintaining self-tolerance and controlling autoimmune responses. Here, we analyzed for the first time the behaviour of Tregs in the context of a stress-induced activation of the adaptive immune response.31 healthy young males underwent a brief laboratory stressor and, in a crossover design, served as their own unstressed controls. We quantified effects of acute stress on CD4(+)FOXP3(+) T regulatory cells and other T cell subpopulations using flow cytometry. In addition, the expression of Treg-related effector molecules and stress hormone receptors were analyzed in the subjects' peripheral T cells.We confirmed our previous observation of a stress-induced decrease in CD45RA(+)CCR7(+) "naive" and CD45RA(-)CCR7(+) "central memory" T cells while CD45RA(-)-CCR7(-) "memory effector" and CD45RA(+)CCR7(-) "terminally differentiated" effector T cells remained stable or increased. Importantly, we found acute psychological stress to cause a concomitant decrease in CD4(+)FOXP3(+) Tregs and in CD4(+) T cells expressing Treg-related effector molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and latency associated peptide (LAP). Finally, we observed beta(1)-adrenergic and glucorticoid a receptors to be overexpressed in Tregs, suggesting that these molecules might mediate stress-related effects on Tregs.In conclusion, inhibiting components of the adaptive immune response, like Tregs, are down-regulated during a stress-induced activation of the adaptive immune response. In situations of chronic stress, this scenario might result in an exacerbation of inflammatory conditions such as autoimmune diseases. (c) 2009 Elsevier Ltd. All rights reserved.